Recieved: 07/08/2024
Accepted: 02/28/2025
Published: 04/09/2025
Keywords: phantom; pain; neuromodulation; reorganization; rehabilitation; neuropathogenesis of PPS
Pages: 24-36
DOI: 10.11621/npj.2025.0202
Available online: 09.04.2025
Shagina, E.D., Nikishina, V.B., Zapesotskaya, I.V. (2025). Neuropathogenesis of Phantom Pain Syndrome: Overview of Foreign Research. National Psychological Journal, 20(2) , 24-36. https://doi.org/10.11621/npj.2025.0202
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CopyBackground. The insufficient systematization of knowledge about PLPS (Phantom Limb Pain Syndrome) and the absence of a coherent pathophysiological theory hinder the development of scientifically-based treatment methods, highlighting the necessity for further research in this area.
Objectives. This study aims to identify, critically analyze, and describe the currently relevant theories and models of the neuro-pathogenesis of PLPS to determine the target areas and methods for PLPS correction.
Study Participants. The primary sample consisted of 170 scientific studies from the fields of psychology, neuropsychology, and cognitive sciences, focusing on the issue of PLPS neuro-pathogenesis.
Methods. Literature search was conducted using the LENS information database. The analysis focused on the works published between 2018 and 2024. The authors employed historical-retrospective and bibliometric analyses.
Results. Based on the analysis of scientific data, the neuropathogenesis of PLPS is explained by three main groups of theories. Peripheral models associate PLPS with pathological changes in the peripheral nervous system, including hyperactivity of damaged axons (neuroma model) and residual nociceptive signals. Central models explain PLPS through somatosensory cortex reorganization (“remapping”), persistent activity of cortical representations of the lost limb (persistent representation model), and the concept of an innate “neuromatrix” that shapes pain perception. Mixed models consider PLPS as a result of interactions between peripheral and central factors, including disturbances in body schema and stochastic processes leading to the development of abnormal neural connections.
Conclusions. Based on the analyzed theories, the authors identified potential targets for rehabilitation interventions in PLPS. This made it possible to identify theoretically justified goals, objectives and areas of work in the correction of PLPS: methods of neuromodulation, techniques aimed at reducing cortical reorganization, implementation of behavioral and cognitive therapies, biofeedback training, and the use of sensory and motor prostheses.
Anderson-Barnes, V.C., McAuliffe, C., Swanberg, K.M., Tsao, J.W. (2009). Phantom limb pain — a phenomenon of proprioceptive memory? Medical Hypotheses, 73(4), 555–558. https://doi.org/10.1016/j.mehy.2009.05.038
Andoh, J., Milde, C., Diers, M., Bekrater-Bodmann, R., Trojan, J., Fuchs, X., Becker, S., Desch, S., Flor, H. (2020). Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective. Scientific Reports, 10, 11504. https://doi.org/10.1038/s41598-020-68206-9
Atemali, A., Katz, J. (2019). Recent advances in understanding and managing Phantom Limb pain. F1000Research, (8), 1167. https://doi.org/10.12688/f1000research.19355.1
Aymerich-Franch, L., Ganesh, G. (2020). The role of body schema in the development of human-machine interfaces. Frontiers in Human Neuroscience, (14), 31–37. https://doi.org/10.3389/fnhum.2020.00038
Bekrater-Bodmann, R., Schredl, M., Diers, M. (2015). Post-amputation pain is associated with the recall of an impaired body representation in dreams — results from a nation-wide survey on limb amputees. PLOS ONE, 10(3), e0119552. https://doi.org/10.1371/journal.pone.0119552
Bromage, P.R., Melzack, R. (1974). Phantom limbs and the body schema. Canadian Anaesthetists’ Society journal, 21(3), 267–274. https://doi.org/10.1007/BF03005731
Brooks, J.C.W., Zambrenni, L., Godinez, A., Craig, A.D., Tracey, I. (2005). Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging. NeuroImage, 27(1), 201–209. https://doi.org/10.1016/j.neuroimage.2005.03.041
Chan, A.W., Bilger, E., Griffin, S., Elkis, V., Weeks, S., Hussey-Anderson, L., Pasquina, P.F., Tsao, J.W., Baker, C.I. (2019). Visual responsiveness in sensorimotor cortex is increased following amputation and reduced after mirror therapy. Neuroimage: Clinical, (23), 101882. https://doi.org/10.1016/j.nicl.2019.101882
Chegurov, O.K., Kolesnikov, S.V., Kolesnikova, E.S., Skripnikov, A.A. (2014). Phantom limb pain syndrome: pathogenesis, treatment, prevention (literature review). Genij ortopedii = Genius of Orthopedics, (1), 89–93. (In Russ.). URL: https://cyberleninka.ru/article/n/fantomno-bolevoy-sindrom-patogenez-lechenie-profilaktika-obzor-literatury (accessed 26.02.2025).
Collins, K.L., Russell, H.G., Schumacher, P.J., Robinson-Freeman, K.E., O’Conor, E.C., Gibney, K.D., Yambem, O., Dykes, R.W., Waters, R.S., Tsao, J.W. (2018). A review of current theories and treatments for Phantom limb pain. Journal of Clinical Investigation, 128(6), 2168–2176. https://doi.org/10.1172/JCI94003
Corbett, M., South, E., Harden, M., Eldabe, S., Pereira, E., Sedki, I., Hall, N., Woolacott, N. (2018). Brain and spinal stimulation therapies for phantom limb pain: a systematic review. Health Technology Assessment, 22(62), 1–94. https://doi.org/10.3310/hta22620
Di Pino, G., Piombino, V., Carassiti, M., Ortiz-Catalan, M. (2021). Neurophysiological models of Phantom Limb Pain: What can be learnt. Minerva Anestesiologica, 87(4). https://doi.org/10.23736/S0375-9393.20.15067-3
Di Vita, A., Boccia, M., Palermo, L., Guariglia, C. (2019). Neural modifications in lower limb amputation: An fMRI study on action and non-action-oriented body representations. Brain Imaging and Behavior, 13(2), 315–327. https://doi.org/10.1007/s11682-018-9956-8
Dumanian, G.A., Potter, B.K., Mioton, L.M., Ko, J.H., Cheesborough, J.E., Souza, J.M., Ertl, W.J., Tintle, S.M., Nanos, G.P., Valerio, I.L., Kuiken, T.A., Apkarian, A.V., Porter, K., Jordan, S.W. (2019). Targeted muscle reinnervation treats neuroma and Phantom Pain in major limb amputees. Annals of Surgery, 270(2), 238–246. https://doi.org/10.1097/SLA.0000000000003088
Flor, H. (2002). Phantom-limb pain: Characteristics, causes, and treatment. The Lancet Neurology, 1(3), 182–189. https://doi.org/10.1016/S1474-4422(02)00074-1
Flor, H., Nikolajsen, L., Jensen, T.S. (2006). Phantom limb pain: A case of maladaptive CNS plasticity? Nature Reviews Neurology, 17(7), 457–468. https://doi.org/10.1038/s41582-021-00490-5
Fuchs, X., Flor, H., Bekrater-Bodmann, R. (2018). Psychological factors associated with Phantom Limb Pain: A Review of recent findings. Pain Research and Management, 1–12. https://doi.org/10.1155/2018/5080123
Giummarra, M.J., Gibson, S.J., Georgiou-Karistianis, N., Bradshaw, J.L. (2007). Central mechanisms in Phantom Limb Perception: The Past, present and future. Brain Research Reviews, 54(1), 219–232. https://doi.org/10.1016/j.brainresrev.2007.01.009
Hahamy, A., Makin, T.R. (2019). Remapping in cerebral and cerebellar cortices is not restricted by Somatotopy. The Journal of Neuroscience, 39(47), 9328–9342. https://doi.org/10.1523/JNEUROSCI.2599-18.2019
Hall, N., Abd-Elsayed, A., Eldabe, S. (2019). Phantom Limb Pain. In: A. Abd-Elsayed, (ed.). Pain. (pp. 193–202). New York: Springer Publ.
Huang, R.-S., Chen, C., Tran, A.T., Holstein, K.L., Sereno, M.I. (2012). Mapping multisensory parietal face and body areas in humans. Proceedings of the National Academy of Sciences, 109(44), 18114–18119. https://doi.org/10.1073/pnas.1207946109
Issa, C.J., Svientek, S.R., Dehdashtian, A. (2022). Pathophysiological and neuroplastic changes in postamputation and neuropathic pain: review of the literature. Plastic and Reconstructive Surgery Global Open, 10, e4549. https://doi.org/10.1097/GOX.0000000000004549
Jones, E.G. (2000). Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex. Annual Review of Neuroscience, 23(1), 1–37. https://doi.org/10.1146/annurev.neuro.23.1.1
Katz, J. (1993). Phantom Limb experience in children and adults: Cognitive and affective contributions. Canadian Journal of Behavioural Science / Revue canadienne des sciences du comportement, 25(3), 335–354. https://doi.org/10.1037/h0078845
Katz, J., Melzack, R. (1990). Pain ‘memories’ in Phantom limbs: Review and Clinical Observations. Pain, 43(3), 319–336. https://doi.org/10.1016/0304-3959(90)90029-D
Kikkert, S., Mezue, M., Henderson Slater, D., Johansen-Berg, H., Tracey, I., Makin, T.R. (2017). Motor correlates of Phantom Limb Pain. Cortex, 95, 29–36. https://doi.org/10.1016/j.cortex.2017.07.015
Kolomentsev, S.V., Polezhaev, P.A., Gaivoronskii, A.I., Kolomentseva, A.V., Tsygan, N.V. (2023). Modern concepts of treatment of phantom limb pain. Vestnik Rossijskoj Voenno-medicinskoj akademii = Bulletin of the Russian Military Medical Academy, 25(3), 515–527. (In Russ.). https://doi.org/10.17816/brmma340914
Kucyi, A., Davis, K.D. (2015). The dynamic pain connectome. Trends in Neurosciences, 38(2), 86–95. https://doi.org/10.1016/j.tins.2014.12.006
Limakatso, K., Bedwell, G.J., Madden, V.J., Parker, R. (2020). The prevalence and risk factors for phantom limb pain in people with amputations: A systematic review and meta-analysis. PLOS ONE, 15(10), e0240431. https://doi.org/10.1371/journal.pone.0240431
Limakatso, K., Ndhlovu, F., Usenbo, A., Rayamajhi, S., Kloppers, C., Parker, R. (2024). The prevalence and risk factors for phantom limb pain: A cross-sectional survey. BMC Neurology, 24(1), 57. https://doi.org/10.1186/s12883-024-03547-w
Lotze, M., Grodd, W., Birbaumer, N., Erb, M., Huse, E., Flor, H. (1999). Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? Nature Neuroscience, 2(6), 501–502. https://doi.org/10.1038/9145
MacIver, K., Lloyd, D.M., Kelly, S., Roberts, N., Nurmikko, T. (2021). Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain, 144(7), 2047–2059. https://doi.org/10.1093/brain/awab110
Makin, T.R., Flor, H. (2020). Brain (re)organisation following amputation: Implications for phantom limb pain. NeuroImage, 218(1), 116943. https://doi.org/10.1016/j.neuroimage.2020.116943
Makin, T.R., Scholz, J., Filippini, N., Henderson Slater, D., Tracey, I., Johansen-Berg, H. (2013). Phantom pain is associated with preserved structure and function in the former hand area. Nature Communications, 4(1), 1570. https://doi.org/10.1038/ncomms2571
Melzack, R. (2020). The neuromatrix theory of pain. PainScale. URL: https://www.painscale.com/article/neuromatrix-theory-of-pain (accessed: 13.03.2025).
Melzack, R. (1990). Phantom limbs and the concept of a neuromatrix. Trends in Neurosciences, 13(3), 88–92. https://doi.org/10.1016/01662236(90)90179-E
Melzack, R. (2001). Pain and the neuromatrix in the brain. Journal of Dental Education, 65(12), 1378–1382. https://doi.org/10.1002/j.0022-0337.2001.65.12.tb03497.x
Merabet, L.B., Rizzo, J.F., Amedi, A., Somers, D.C., Pascual-Leone, A. (2019). Neural reorganization following sensory loss: The opportunity of change. Nature Reviews Neuroscience, 20(12), 613–624. https://doi.org/10.1038/s41583-019-0201-3
Ortiz-Catalan, M. (2018). The stochastic entanglement and Phantom Motor Execution hypotheses: A theoretical framework for the origin and treatment of Phantom Limb Pain. Frontiers in Neurology, 9, 748. https://doi.org/10.3389/fneur.2018.00748
Ramachandran, V.S., Rogers-Ramachandran, D.C. (1996). Synaesthesia in phantom limbs induced with mirrors. Proceedings of the Royal Society B: Biological Sciences, 263(1369), 377–386. https://doi.org/10.1098/rspb.1996.0058
Richardson, C., Crawford, K., Milnes, K., Bouch, E., Kulkarni, J. (2015). A clinical evaluation of postamputation phenomena including phantom limb pain after lower limb amputation in dysvascular patients. Pain Management Nursing, 16(4), 561–569. https://doi.org/10.1016/j.pmn.2014.10.006
Sayko, A.V. (2018). Current situation with the problem of phantom pain. Mezhdunarodnyj nevrologicheskij zhurnal = International Neurological Journal, 4(98), 84–95. (In Russ.). https://doi.org/10.22141/2224-0713.4.98.2018.139430
Sherman, R.A., Bruno, G.M. (1987). Concurrent variation of burning phantom limb and stump pain with near surface blood flow in the stump. Orthopedics, 10(10), 1395–1402. https://doi.org/10.3928/0147-7447-19871001-09
Sinha, R., Van Den Heuvel, W.J. (2011). A systematic literature review of quality of life in lower limb amputees. Disability and Rehabilitation, 33(11), 883–899. https://doi.org/10.3109/09638288.2010.514646
Subedi, B., Grossberg, G.T. (2021). Phantom limb pain: mechanisms and treatment approaches. Pain Research and Treatment, 864605. https://doi.org/10.1155/2021/864605
Treede, R.-D., Meyer, R.A., Raja, S.N., Campbell, J.N. (1992). Peripheral and central mechanisms of cutaneous hyperalgesia. Progress in Neurobiology, 38(4), 397–421. https://doi.org/10.1016/0301-0082(92)90027-C
Vassallo, M., Picozzi, M., Parati, E.A. (2023). An overview of the body schema and body image: Theoretical models, methodological settings and pitfalls for rehabilitation of persons with neurological disorders. Brain Sciences, 13(10), 1410. https://doi.org/10.3390/brainsci13101410
Woo, S.L., Kung, T.A., Brown, D.L., Leonard, J.A., Kelly, B.M., Cederna, P.S. (2016). Regenerative peripheral nerve interfaces for the treatment of postamputation neuroma pain: A pilot study. Plastic and Reconstructive Surgery — Global Open, 4(12), e1038. https://doi.org/10.1097/GOX.0000000000001038
Zeharia, N., Hertz, U., Flash, T., Amedi, A. (2012). Negative blood oxygenation level dependent homunculus and somatotopic information in primary motor cortex and supplementary motor area. Proceedings of the National Academy of Sciences, 109(45), 18565–18570. https://doi.org/10.1073/pnas.1119125109
Zeharia, N., Hertz, U., Flash, T., Amedi, A. (2015). New whole-body sensory-motor gradients revealed using phase-locked analysis and verified using multivoxel pattern analysis and functional connectivity. The Journal of Neuroscience, 35(7), 2845–2859. https://doi.org/10.1523/JNEUROSCI.4246-14.2015
Shagina, E.D., Nikishina, V.B., Zapesotskaya, I.V.. Neuropathogenesis of Phantom Pain Syndrome: Overview of Foreign Research. // National Psychological Journal 2025. 2. Pages24-36. doi: 10.11621/npj.2025.0202
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